Norepinephrine (NE) is a likely key neurotransmitter for normal brain-pituitary-gonadal function. For example, administration of NE antagonists suppress pulsatile gonadotropin-releasing hormone (GnRH) secretion in the ovariectomized (OVX) rhesus monkey and block coitus-induced ovulation in the rabbit. Direct measurement of hypothalamic NE release has been technically difficult. However, our laboratory has perfected microdialysis (fD) and assay procedures to collect and measure continuous intrahypothalamic NE and GnRH secretions in both monkeys and rabbits. We have utilized these techniques to monitor changes in hypothalamic NE secretion during an estradiol-17 (E)-induced GnRH surge in the monkey, and after a coitally induced GnRH surge in the rabbit. E-treated OVX monkeys (circulating E maintained between 30-90 pg/ml) were subjected to fD with continuous sample collections at 20-min intervals for 40 h. Additional estrogen (42 fg estradiol benzoate [EB]/kg body weight subcutaneously, s.c.) was given at h5. This EB treatment is known to induce a luteinizing hormone (LH) surge 24-48 h after administration. Concentrations of NE in fD samples did not change during the first 22 h of fD (4 h before to 18 h after EB), but NE levels increased between 24- to 30-h and were sustained to h40 at levels 30- to 150-fold higher than pre-EB values. This incremental pattern of NE release resembles the pattern of the GnRH surge in intact monkeys (Endocrinology 133:1650, 1993); however, neither fD-GnRH levels nor plasma LH values increased in these OVX+E animals. In fact, these levels were low initially and did not change following s.c. EB administration. These findings are not in accord with numerous earlier studies; therefore, the role of the dramatic increase in hypothalamic NE release induced by s.c. EB cannot be ascertained at the present time. In New Zealand White female rabbits, fD samples were collected at 2.5-min intervals for 4 h. Natural mating with male partners occurred at the beginning of the third hour. Concentrations of NE in brain fD samples from females increased within 5 min of coitus, whereas increased GnRH values were observed later, i.e., at 7.5-10 min after coitus. In contrast, neither NE nor GnRH increased in male rabbits after coitus. These data suggest that NE may be an integral signal between coitus and the GnRH surge in the female. The findings that coitus in males activated neither neurochemical implies a clear gender difference in this neuroendocrine axis.